Although effective antiretroviral therapy (ART) has significantly increased the life expectancy of people with HIV, viral rebound almost always occurs following cessation of therapy. In addition, chronic treated HIV infection is associated with increased risk of non-AIDS associated chronic diseases, and lifelong ART entails a high economic burden especially for low and middle-income countries. As such, evaluation of strategies leading to the eradication or functional cure of HIV ART remain a top priority in HIV research. These strategies include immunotherapeutic interventions, such as therapeutic vaccines, that aim to boost HIV-specific immune responses with a goal of controlling viral replication following treatment interruption.

Previous studies on HIV pathogenesis and HIV elite controllers have shown the importance of T cell responses in the control of viral replication. As such, there have been several clinical trials focusing on novel therapeutic vaccine approaches that aim to boost these T cell responses. However, despite promising results in a number of studies, the goal of achieving HIV remission off ART through these vaccines has remained elusive. Ongoing studies have been investigating various factors that could affect the immunogenicity of these vaccines including the type of vaccines and immunogens used, the specific HIV epitopes targeted, the effect of immunoregulatory cells and pathways, the correlates of protection, and even the clinical trial study design. Indeed, the past few years have ushered in novel techniques and concepts with the objective of developing and optimizing the next generation of T cell therapeutic vaccines.

In this Research Topic, we aim to present studies focusing on the various factors affecting efficacy of therapeutic T cell vaccines. These include:

• Novel vaccine delivery methods and vaccine design
• Identification of immunogenic HIV epitopes that can be targeted by the vaccines
• Optimized strategies with combination immunotherapies
• Novel assays to evaluate vaccine responses and correlates of protection
• The role of immunoregulatory or inhibitory pathways in therapeutic vaccine studies and approaches to address them
• Innovative T cell vaccine clinical trial designs

We welcome the submission of Original Research articles, Methods articles, Reviews, Mini-reviews and Clinical Trial articles covering any of the above subtopics.

Dr. Rinaldo holds a patent related to HIV immunotherapies. The other Topic Editors declare no conflict of interest with regards to the Research Topic theme.

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